This proposal aims to develop a new generation of high-speed, low-cost, microelectromechanical systems vertical cavity surface emitting lasers (MEMS-VCSELs) for optical coherence tomography (OCT) at multi-MHz axial scan rates. The proposed effort involves a collaboration between Praevium Research, with expertise in MEMS-VCSEL development, and the Massachusetts Institute of Technology (MIT), a leader in OCT system integration and OCT imaging. These ultrahigh speed imaging systems enable new in vivo fundamental and clinical imaging applications, at larger fields of view and finer resolutions than were previously possible. Multi- MHz operation is particularly critical for advancing OCT in cancer studies, which require high speed for large volume imaging of microstructure, and dense sampling for angiographic imaging (OCTA) and optical coherence microscopy (OCM). The proposed low-cost laser will make these high performance technologies widely available to the fundamental and clinical cancer research communities. Praevium Research will focus on the development of the new high-speed, low-cost MEMS-VCSEL swept laser source. MEMS-VCSELs have recently emerged as a near ideal laser for OCT. These devices offer a unique combination of wide tuning range, high and variable tuning speed, dynamic single mode operation enabling meter-scale imaging range, and the potential for low-cost, enabled by monolithic wafer-scale fabrication and testing. The proposed work seeks to push MEMS-VCSEL technology to 2-5MHz axial scan rates in a monolithic design, with multiple approaches to actuator design and packaging to optimize laser speeds, tuning range, and sweep linearity. These efforts will significantly reduce manufacturing cost, providing the first volume-scalable, commercially available swept source for multi-MHz OCT, to enable a 10x-40x speed improvement over existing commercial OCT instruments at a fraction of the cost of current swept source technologies. MIT will integrate the new light source with state of the art data acquisition and processing and with new endoscopic probe technology to demonstrate in vivo imaging in patients with gastrointestinal pathologies. New ultrahigh speed OCT system designs involving laser sweep multiplexing and linearization, and low latency OCT processing and display, will be investigated for performance and feasibility. Micromotor probes, tethered capsules, and piezoelectric scanners will be developed for compact and high-precision optical imaging. MIT will demonstrate endoscopic applications of these technologies in pre-clinical studies, while investigating system parameters and designs for optimized performance to establish workflow and imaging protocols for potential future clinical applications. In an existing collaboration with the Boston Veterans Affairs Medical Center, MIT will further demonstrate studies in patients with upper and lower gastrointestinal tract pathologies, assessing capabilities for wide field coverage of mucosal structure and vasculature, and cellular morphology. These efforts will motivate development in many other endoscopic, laparoscopic, or surgical applications.